sembragiline (RO4602522) / Roche, Evotec - LARVOL DELTA

Generation of two iPSC lines with pathogenic DMD nonsense mutations c.4729C>T and c.5713G>T. (PubMed, Stem Cell Res) - "Here, we describe the generation of two isogenic induced pluripotent stem cell (iPSC) lines engineered using CRISPR-Cas12 to introduce specific nonsense mutations in the DMD gene: c.4729C>T (p.Arg1577Ter) and c.5713G>T (p.Arg1905Ter). The edited iPSC lines retain normal karyotypes, express key pluripotency markers, and exhibit the capacity to differentiate into derivatives of all three germ layers. These models provide powerful tools for investigating DMD pathogenesis, uncovering mechanisms of genetic compensation, and evaluating potential therapeutic strategies."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • ARG1

Development and Clinical Application of Positron Emission Tomography Imaging Agents for Monoamine Oxidase B. (PubMed, Front Neurosci) - "Important applications of [C]L-deprenyl-D2 PET are detecting a 40% loss in radiotracer accumulation in cigarette smokers, and substantial occupancy of novel therapeutics like EVT301 and sembragiline. Given the number of diseases with elevations of MAO-B density and astrogliosis, and the advance of [C]SL25.1188, clinical applications of MAO-B imaging are still at an early stage."

Journal • Review • Addiction (Opioid and Alcohol) • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Depression • Huntington's Disease • Major Depressive Disorder • Mental Retardation • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

Synthesis and evaluation of biaryl derivatives for structural characterization of selective monoamine oxidase B inhibitors toward Parkinson's disease therapy. (PubMed, Bioorg Med Chem) - "In addition, 12c showed greater MAO-B inhibitory activity and selectivity compared to well-known MAO-B inhibitors such as selegiline, safinamide and sembragiline. In the MPTP-induced mouse model of Parkinson's disease (PD), 12c significantly protected the tyrosine hydroxylase (TH)-immunopositive DAergic neurons and attenuated the PD-associated behavioral deficits. This study suggests characteristic structures as a MAO-B inhibitor that may provide a good insight for the development of therapeutic agents for PD."

Journal • Biosimilar • Gene Therapies • Parkinson's Disease

Roche - Pipeline summary (Roche Press Release) - Sembragiline in Phase 2 for Alzheimer's disease removed from Roche's pipeline.

Discontinued • Alzheimer's Disease

Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD). (PubMed) - J Alzheimers Dis - P2; "This study showed that sembragiline was well-tolerated in patients with moderate AD. The study missed its primary and secondary endpoints. Post hoc analyses suggested potential effect on neuropsychiatric symptoms and functioning in more behaviorally impaired study population at baseline."

Journal • Alzheimer's Disease • Biosimilar